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Updated: Aug 4, 2026
Isolation of Mouse Respiratory Epithelial Cells and Exposure to Experimental Cigarette Smoke at Air Liquid Interface
Published on: February 21, 2011
Knockout of RAGE ameliorates mainstream cigarette smoke-induced airway inflammation in mice
Mei Chen1, Tao Wang2, Yongchun Shen3
1Department of Respiratory Medicine, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, PR China; Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China.
Background:
The receptor for advanced glycation end products (RAGE), a multiligand receptor, has been proved to be implicated in inflammatory responses in chronic obstructive pulmonary disease (COPD). In this study, we investigated the role of RAGE in cigarette smoke (CS)-induced airway inflammation in COPD.
Methods:
Wild-type (WT) and RAGE gene knockout (KO) mice were exposed to mainstream CS or room air for 2h twice daily, 6days per week for consecutive 4weeks. Cell counts and proinflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). Lung tissues were collected for histological examination and gene expression profiling by cDNA microarray.
Results:
CS exposure induced significant airway inflammation in WT mice evidenced by histological inflammatory changes in HE stain with increased neutrophils and proinflammatory cytokines in the BALF, which were all attenuated by RAGE KO. cDNA microarray indicated a total of 179 upregulated genes and 351 downregulated genes in mouse lungs. Among these genes, S100 proteins (S100A8 and S100A9), the RAGE common ligands, were significantly downregulated, which were validated by real-time qPCR. Further analyses by Gene Ontology, KEGG and Disease Ontology suggested these differentiated expressed genes significantly related to the immune-inflammatory responses in lungs via crosstalking with a complicated network of signaling pathways.
Conclusions:
Knockout of RAGE significantly ameliorates mainstream CS-induced airway inflammation in mice possibly via downregulating S100A8/A9 expression and its related immune-inflammatory responses.
